Extensive contact between blood and synthetic surfaces during extracorporeal circulation results in profound alterations in circulating cells and plasma proteins. Thus activation of prekallikrein, the complement system, platelets and leucocytes may occur. Since platelets, leucocytes and these enzyme systems may influence local blood flow, alter vascular permeability and participate in the inflammatory response, an understanding of the behavior of blood at the synthetic surface interface is clinically important. Using simulated extracorporeal circulation, we plan to extend our observations identifying constitutents released from platelets and leucocytes and determine the extent of activation of the prekallikrein and complement systems. Utilizing spectrofluorimetic assays, released lysosomal hydrolases will be quantitated and the extent of the platelet and leucocyte release reaction determined. Prekallikrein activation will be monitored by a spectrophotometric assay and complement conversion detected by radioimmunoassay specific for C3B. Following delineation of the extent of activation of these systems, pharmacological intervention will be employed to alter the pattern of release (e.g., Prostaglandin I2 for cellular inhibition). Finally the effects of this altered blood on the pulmonary system will be determined using an isolated, in situ canine lung model with serial determinations of pulmonary vascular resistance, respiratory mechanics and arterial blood gasses. Extravascular lung water and the efficacy of cellular inhibitors as pulmonary preservative agents will be evaluated.